The epidemiology of sickle cell disease in children recruited in infancy in Kilifi, Kenya: a prospective cohort study
The epidemiology of sickle cell disease in children recruited in infancy in Kilifi, Kenya: a prospective cohort study
复制标题
DOI：
10.1016/s2214-109x(19)30328-6
复制
发表时间：
2019-10-01
影响因子：
34.3
通讯作者：
Williams, Thomas N.
中科院分区：
文献类型：
--
作者：
Uyoga, Sophie;Macharia, Alex W.;Williams, Thomas N.
背景镰状细胞病是人类最常见的严重单基因疾病。在非洲，50-90% 出生时患有镰状细胞病的儿童在五岁生日前死亡。在这项研究中，我们旨在描述居住在肯尼亚基利菲地区的出生至 5 岁患有和不患有镰状细胞病的儿童的特定临床结果的比较发生率。 方法 这项前瞻性队列研究是对肯尼亚印度洋沿岸的基利菲遗传出生队列研究 (KGBCS) 的成员进行的。该研究的招募是通过基利菲健康和人口监测系统（KHDSS）进行的，该系统覆盖了 26 万名常住人口，招募时间为 2006 年 1 月 1 日至 2011 年 4 月 30 日。所有在 KHDSS 地区出生且在招募期间年龄为 3 至 12 个月的儿童都有资格入选。参与者接受了镰状细胞病检测，并通过被动监测跟踪生存状况和因疾病而入院的基利菲县医院，直到他们五岁生日。患有镰状细胞病的儿童在专门的门诊诊所接受了确认性检测和护理。结果显示，KGBCS 成功招募了 15 737 名婴儿，其中 128 名（0.8%）婴儿患有镰状细胞病，其中 70 名（54.7%）在招募后 12 个月内在门诊就诊。患有镰状细胞病的儿童的死亡率（每 1000 人年观察 58 例，95% CI 40-86）高于没有镰状细胞病的儿童（每 1000 人年观察 2.4 例，2.0-2-8；调整后的发病率比 [IRR] 23.1，95% CI 15.1-35.3）。在患有镰状细胞病的儿童中，在诊所登记的儿童（调整后的 IRR 0.26，95% CI 0.11-0.62）和血红蛋白 F 水平较高的儿童（HbF；调整后的 IRR 0.40，0.17-0.94）死亡率较低。患有镰状细胞病的儿童的入院率也高于没有镰状细胞病的儿童（每 1000 人年观察 210 例，95% CI 174-253，而每 1000 人年观察 43 例，42-45；调整后 IRR 4.80，95% CI 3.84-6.15）。镰状细胞病患者入院的最常见原因是严重贫血（每 1000 人年观察中发生率为 48，95% CI 32-71）。招募 HbF 水平高于中位数的患者 (IRR 0.43, 95% CI 0.24-0 .78; p=0.005) 和 α-地中海贫血纯合子患者 (0.07, 0.01-0.83; 1)=0.035) 入院率较低。解释 尽管本研究中患有镰状细胞病的幼儿发病率和死亡率较高肯尼亚队列中，两者均因早期诊断和支持性护理而减少。现在的重点必须转向早期发现和预防镰状细胞病的长期并发症。版权所有 (C) 2019 作者。由爱思唯尔有限公司出版
Background Sickle cell disease is the most common severe monogenic disorder in humans. In Africa, 50-90% of children born with sickle cell disease die before they reach their fifth birthday. In this study, we aimed to describe the comparative incidence of specific clinical outcomes among children aged between birth and 5 years with and without sickle cell disease, who were resident within the Kilifi area of Kenya.Methods This prospective cohort study was done on members of the Kilifi Genetic Birth Cohort Study (KGBCS) on the Indian Ocean coast of Kenya. Recruitment to the study was facilitated through the Kilifi Health and Demographic Surveillance System (KHDSS), which covers a resident population of 260 000 people, and was undertaken between Jan 1, 2006, and April 30, 2011. All children who were born within the KHDSS area and who were aged 3-12 months during the recruitment period were eligible for inclusion. Participants were tested for sickle cell disease and followed up for survival status and disease-specific admission to Kilifi County Hospital by passive surveillance until their fifth birthday. Children with sickle cell disease were offered confirmatory testing and care at a dedicated outpatient clinic.Findings 15 737 infants were recruited successfully to the KGBCS, and 128 (0.8%) of these infants had sickle cell disease, of whom 70 (54.7%) enrolled at the outpatient dinic within 12 months of recruitment. Mortality was higher in children with sickle cell disease (58 per 1000 person-years of observation, 95% CI 40-86) than in those without sidde cell disease (2.4 per 1000 person-years of observation, 2.0-2-8; adjusted incidence rate ratio [IRR] 23.1, 95% CI 15.1-35.3). Among children with sickle cell disease, mortality was lower in those who enrolled at the clinic (adjusted IRR 0.26, 95% CI 0.11-0.62) and in those with higher levels of haemoglobin F (HbF; adjusted IRR 0.40, 0.17-0.94). The incidence of admission to hospital was also higher in children with sickle cell disease than in children without sidde cell disease (210 per 1000 person-years of observation, 95% CI 174-253, vs 43 per 1000 person-years of observation, 42-45; adjusted IRR 4.80, 95% CI 3.84-6.15). The most common reason for admission to hospital among those with sickle cell disease was severe anaemia (incidence 48 per 1000 person-years of observation, 95% CI 32-71). Admission to hospital was lower in those with a recruitment HbF level above the median (IRR 0.43, 95% CI 0.24-0 .78; p=0.005) and those who were homozygous for alpha-thalassaemia (0.07, 0.01-0.83; 1)=0.035).Interpretation Although morbidity and mortality were high in young children with sickle cell disease in this Kenyan cohort, both were reduced by early diagnosis and supportive care. The emphasis must now move towards early detection and prevention of long-term complications of sickle cell disease. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.